This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Biomolecules in the cell interact with numerous partners, including small organic molecules called osmolytes that affect their stability. Some well-known osmolytes such as urea and guandinium chloride are known to destabilize proteins, RNA, and DNA molecules, but TMAO has notably demonstrated to stabilize proteins. The effects of TMAO on RNA molecules have not been thoroughly explored even though changes in stabilities of RNA molecules can profoundly affect a number of cellular functions that include gene expression, transcription, and splicing reactions, just to name a few. Recent experimental studies by Lamber and Draper (JMB, 2007) showed that the secondary structures of RNA are destabilized but the tertiary interactions are stabilized by TMAO. They hypothesized that the destabilization of the secondary structures is a result of preferential accumulation of osolytes around base groups and depletion around the ribose-phosphate backbone. In our present proposed study, we plan on studying the effect of TMAO interactions with RNA hairpins to microscopically test the hypotheses put forth by Lambert and Draper's study. Specifically, we will use all-atom MD simulations using the CHARMM and AMBER force fields to determine the preferred interactions of TMAO with the specific base, sugar, and phosphate moieties of RNA. We will use the NAMD MD program to run our simulations because a) it has been demonstrated to scale well will parallelization and b) it can support both the CHARMM and AMBER force fields making a direct comparison possible.